Process for the preparation of N-alkylhalogenoanilines

ABSTRACT

A process for the preparation of N-alkylhalogenoanilines of the formula (I) 100° ##STR1## in which X is a chlorine or bromine atom and n is the number 1 or 2, R 1  is an alkyl (C 1  -C 4 ) radical, R 2  an alkyl (C 1  -C 6 ) radical or R 1  and R 2  together with the carbon atom can form a five- or six-membered cycloalkane ring, by reacting a halogenonitrobenzene of the formula (II) ##STR2## in which X and n have the abovementioned meanings with an at least stoichiometric amount of a carbonyl compound of the formula (III) ##STR3## in which R 1  and R 2  have the meanings mentioned or R 1  and R 2  together with the carbon atom of the carbonyl group can form a five- or six-membered cycloalkane ring, in an inert organic solvent at temperatures of about 10 to about 100° C., at a hydrogen superatmospheric pressure of about 0 to about 50 bar, in the presence of a platinum catalyst on activated carbon.

The present invention relates to an ecologically and economicallyimproved process for the preparation of N-alkylhalogenoanilines byreductive alkylation of nitrohalogenobenzenes, in particular thepreparation of N-isopropyl-4-chloroaniline by reductive alkylation ofp-nitrochlorobenzene with acetone in the presence of a sulfited platinumcatalyst of defined specific activity.

The problem of halogen elimination which occurs in the catalytichydrogenation of halogen-containing nitro aromatics is also especiallyimportant in reductive alkylations of halogen-containing nitro or aminoaromatics, in particular in industrial processes.

There has therefore not been a lack of attempts to avoid thedisadvantages which occur in reductive alkylation of halogen-containingnitro aromatics or anilines, such as halogen elimination, ringhydrogenation or polyalkylation.

The prior art closest to the process according to the invention isdescribed in German Offenlegungsschrift 2,941,070 A1. The processdescribed there comprises reacting a halogenoaniline orhalogenonitrobenzene with 1 to 10 equivalents of an aliphatic carbonylcompound in an inert solvent, but preferably in a solution of thehalogenoaniline or of the nitro aromatic in the aliphatic carbonylcompound, using 0.05 to 2.0% by weight of a sulfited platinum/carboncatalyst at temperatures of 70 to 120° C., preferably at 80° to 100° C.The hydrogen superatmospheric pressure employed in this process is 40 to100 bar. The yields of N-halogenoalkylanilines are about 95% of theoryat a purity of mostly over 98%.

"Virtually no halogen elimination is observed" in this process, althoughno analytical investigations of halogen elimination are mentioned.

The closest prior art furthermore includes the process described in U.S.Pat. No. 3,350,450 for the preparation of aromatic amines by catalytichydrogenation of aromatic nitro compounds, in particular ofN-alkylhalogenoanilines by reductive alkylation of halogenoanilines orhalogenonitrobenzenes in a one- or two-stage process, using hydrogen andaliphatic aldehydes or ketones in the presence of palladium, platinum,rhodium, ruthenium or cobalt sulfides.

In the abovementioned U.S. patent, the following reaction conditions forthe preparation of N-isopropyl-4-chloroaniline from p-nitrochlorobenzeneand acetone are mentioned: reaction temperature 160° to 200° C.,hydrogen pressure about 70 to 110 bar. Depending on the metal sulfidecatalyst used, the reaction times are 15 minutes to 6.5 hours. Theyields of N-alkylhalogenoaniline are 92.5 to 100%.

The two processes of the closest prior art mentioned have in common thatthe substrate used (halogenonitro aromatic or halogenoaniline) isreacted in a 15- to 10-molar excess of the carbonyl compound. As aresult of the drastic reaction conditions employed, a significantportion of the carbonyl compound which is used as solvent ishydrogenated to the corresponding alcohol. This means, on the one hand,increased consumption of hydrogen, and, on the other hand, that theresulting alcohol/carbonyl compound mixture can only be separated bydistillation with the use of large amounts of energy. Furthermore, thealcohol formed cannot be reintroduced into the continuous process cyclebut has to be disposed of, for example, by introducing it into anotherprocess. Both processes have the additional disadvantage that they mustbe carried out at relatively high reaction temperatures to obtainacceptable reaction times and thus space-time yields.

In contrast, it has now been found that N-alkylhalogenoanilines of thegeneral formula (I) ##STR4## in which X is a chlorine or bromine atomand n is the number 1 or 2, R¹ is a linear or branched alkyl (C₁ -C₄)radical, R² a linear or branched alkyl (C₁ -C₆) radical or R¹ and R²together with the carbon atom to which they are bound can form a five-or six-membered cycloalkane ring, can be prepared in an advantageousmanner, while avoiding the shortcomings of the known processesmentioned, by reacting a halogenonitrobenzene of the general formula(II) ##STR5## in which X and n have the abovementioned meanings with anat least stoichiometric amount of a carbonyl compound of the generalformula (III) ##STR6## in which R¹ and R² have the abovementionedmeanings or R¹ and R² together with the carbon atom of the carbonylgroup can form a five- or six-membered cycloalkane ring, in an organicsolvent which is inert towards the reactants under the reactionconditions at temperatures of about 10° to about 100° C., preferablyabout 30° to about 50° C., at a hydrogen superatmospheric pressure ofabout 0 to about 50 bar, preferably about 5 to about 25 bar, in thepresence of a sulfited platinum catalyst on activated carbon.

Examples of halogenonitrobenzenes of the general formula II mentioned,which can be used, are p-nitrochlorobenzene, o-nitrochlorobenzene,p-bromonitrobenzene, 2,5-dichloronitrobenzene, 3,4-dichloronitrobenzene,3,5-dichloronitrobenzene, 2,4-dichloronitrobenzene or2,3-dichloronitrobenzene.

Examples of suitable carbonyl compounds of the general formula IIImentioned are acetone, diethyl ketone, methyl ethyl ketone, methylisobutyl ketone, methyl isopropyl ketone, ethyl amyl ketone, ethylisoamyl ketone, cyclopentanone or cyclohexanone. The carbonyl compoundsare used in a one- to about 1.5-fold stoichiometric amount, relative tothe halogenonitrobenzene. Although the use of a larger amount ispossible, this does not have any additional positive effect but makesthe process increasingly uneconomical.

Examples of inert solvents which can be used in the process according tothe invention are methanol, ethanol, isopropanol, isobutanol, ethylacetate, n-butyl acetate, isopropyl acetate, isoamyl alcohol or2-ethylhexanol. Preferably, the reaction is carried out in alkylacetates, such as ethyl acetate, n-butyl acetate or isopropyl acetate.

The platinum catalyst used in the process according to the invention isparticularly important. It is a commercially available catalyst (DEGUSSAtype F1OP, 5% by weight of platinum on activated carbon), which has beensulfited, i.e. deactivated, by a process described in German Patent2,105,780. The catalyst is used in the process according to theinvention in amounts of about 2 to about 10 percent by weight,preferably about 3 to about 5 percent by weight, relative to thehalogenonitro compound. In serial tests carried out using the processaccording to the invention, the catalyst used is recycled up to 10 timeswithout replenishing losses due to workup, its activity remainingconstant.

Advantageously, the detailed procedure of the process according to theinvention is as follows: 1 mole of a halogenated nitrobenzene is reactedin an inert organic solvent, preferably an alkyl acetate, such as, forexample, ethyl acetate or in particular n-butyl acetate, over a sulfitedplatinum catalyst in the presence of an excess of about 20 mole percentof an aliphatic ketone of the formula III at a maximum temperature of50° C. and a hydrogen pressure of about 5 to about 25 bar. After thereaction is complete, the platinum catalyst is filtered off, and thesolvent used is distilled off in vacuo. The residue is fractionated invacuo. The N-alkylhalogenoanilines thus obtained usually have a purityof >99%. The catalyst used can be recycled without any loss in yield.

The advantages of the process according to the invention are a smalleramount of the aliphatic carbonyl compound used, a substantially lowerreaction temperature in the reductive alkylation and an almost unlimitedrecycling of the solvent and catalyst used. In this process, except forthe water of the hydrogenation reaction, no waste water is formed. Dueto the low COD, the water formed by hydrogenation is highlybiodegradable.

In the process according to the invention, the halogen elimination is 0to not more than 1%, as detected by GC/MS. At reaction temperatureshigher than 55° C. and also at higher hydrogen pressures such as, forexample, 40 to 60 bar, considerably more halogen elimination wasobserved in some cases. For this reason, more drastic reactionconditions than the ones given are rather a disadvantage in the processaccording to the invention.

In principle, the reductive alkylation can also be carried out with thehalogenoanilines which correspond to the halogenonitrobenzenes of theformula II. However, some of these aniline derivatives are hazardous dueto their physiological properties, and require an additional processstep for their preparation from the corresponding nitro compounds.

The N-alkylhalogenoanilines obtainable by the process are valuablestarting materials and intermediates for the preparation ofplant-protection agents and pharmaceuticals and valuable couplingcomponents for the preparation of azo dyes.

The examples which follow are intended to illustrate the processaccording to the invention in more detail, without limiting it thereto.

EXAMPLE 1

2500 ml of n-butyl acetate and 397.7 g (2.5 mol) of technically purep-nitrochlorobenzene and 175.7 g (3.0 mol) of acetone were initiallyintroduced at room temperature into a 5-liter stainless steelhydrogenation autoclave. After the addition of 15.0 g of sulfitedplatinum catalyst (water content of the catalyst about 50%), theautoclave was flushed 3 times with nitrogen, and then 10 bar of hydrogenwere injected at room temperature. The mixture was then hydrogenated ata temperature of <50° C. and a hydrogen pressure of 5 to 10 bar forabout 1 hour. The hydrogen pressure was then increased to 25 bar, andstirring at 45° to 50° C. and a pressure of 20 to 25 bar was continuedfor 6 hours.

For workup, the autoclave was emptied and rinsed with 150 ml of n-butylacetate, the catalyst was separated off through a filter and washedtwice with 25 ml each of butyl acetate. The catalyst was moistened with7.5 ml of water and stored for the next batch.

The filtrate was concentrated by distillation at about 13 mbar. Theresidue was then distilled in vacuo at 24 to 27 mbar through a packedcolumn to give 372 g of N-isopropyl-4-chloroaniline, which distilledover at a boiling point of 122° to 127° C.

EXAMPLE 2

397.7 g (2.5 mol) of o-nitrochlorobenzene were reacted according to theprocedure described in Example 1. The yield was 89% of theory at apurity of 99.0% (GC).

EXAMPLE 3

Analogously to Example 1, 397.7 g (2.5 mol) of p-nitrochlorobenzene werereacted in 2500 ml of ethyl acetate. The workup was carried out inprinciple analogously, except that the solvent was distilled off atatmospheric pressure and the residue was then likewise fractionated invacuo.

EXAMPLE 4

Analogously to Example 1, 397 g (2.5 mol) of o-nitrochlorobenzene werereacted in 2500 ml of methanol. N-Isopropyl-2-chloroaniline was obtainedby the workup described in Example 3 in a yield of 85% of theory at apurity of 98.7 [sic].

EXAMPLE 5 Comparison Example

Example 1 is repeated, except that the reductive alkylation is carriedout at 100° C. and 40 to 60 bar hydrogen pressure, to give 344.0 g ofN-isopropyl-4-chloroaniline, which corresponds to a yield of 70% oftheory. In addition, 56.7 g of N-isopropylaniline are obtained, which isequivalent to a chlorine elimination of 14%.

EXAMPLE 6

480.0 g (2.5 mol) of 3,4-dichloronitrobenzene were reacted in 2500 ml ofbutyl acetate under the reaction conditions described in Example 1 with10 g of sulfited platinum catalyst F1OP. After the solvent had beendistilled off in vacuo, the residue was fractionated to give 431.0 g ofN-isopropyl-3,4-dichloroaniline at a purity of 98.9% (GC) in the boilingrange 143° to 148° C. (13.33 to 16 bar), which corresponds to a yield of84.5% of theory.

In J. Amer. Chem. Soc. 87, 2767-2768, the suitability of the sulfides ofplatinum metals as catalysts in the hydrogenation of nitrobenzene toaniline is described. In addition, the further important use of thecatalysts in question in the reduction of halogen-containing nitrocompounds to give amines, without occurrence of dehalogenation, ismentioned there. It is additionally mentioned there that the sulfides ofplatinum metals can be used for the reductive alkylation of aliphaticamines or their nitroalkane precursors with aliphatic ketones.

We claim:
 1. A process for the preparation of N-alkylhalogenoanilines ofthe general formula (I) ##STR7## in which X is a chlorine or bromineatom and n is the number 1 or 2, R¹ is a linear or branched alkyl (C₁-C₄) radical, R² a linear or branched alkyl (C₁ -C₆) radical or R¹ andR² together with the carbon atom to which they are bound can form afive- or six-membered cycloalkane ring, which comprises reacting ahalogenonitrobenzene of the general formula (II) ##STR8## in which X andn have the abovementioned meanings with 1 to 1.5 times thestoichiometric amount of a carbonyl compound of the general formula(III) ##STR9## in which R¹ and R² have the abovementioned meanings or R¹and R² together with the carbon atom of the carbonyl group can form afive- or six-membered cycloalkane ring, in an organic solvent which isinert towards the reactants under the reaction conditions attemperatures of 30° to 50° C., at a hydrogen superatmospheric pressureof about 0 to about 50 bar, in the presence of a sulfited platinumcatalyst on activated carbon.
 2. The process as claimed in claim 1,wherein the reaction is carried out at a hydrogen superatmosphericpressure of about 5 to about 25 bar.
 3. The process as claimed in claim1, wherein the reaction is carried out in the presence of 2 to 10percent by weight of platinum catalyst on carbon, relative to thehalogenonitrobenzene used.
 4. The process as claimed in claim 1 whereinthe reaction is carried out in the presence of 3 to 5 percent by weightof platinum catalyst on carbon, relative to the halogenonitrobenzeneused.
 5. The process as claimed in claim 1 wherein thehalogenonitrobenzene used is p-nitrochlorobenzene, o-nitrochlorobenzene,p-bromonitrobenzene, 2,5-dichloronitrobenzene, 3,4-dichloronitrobenzene,3,5-dichloronitrobenzene, 2,4-dichloronitrobenzene or2,3-dichloronitrobenzene.
 6. The process as claimed in claim 1 whereinacetone, diethyl ketone, methyl ethyl ketone, methyl isobutyl ketone,methyl isopropyl ketone, ethyl amyl ketone, ethyl isoamyl ketone,cyclopentanone or cyclohexanone is used as the carbonyl compound.
 7. Theprocess as claimed in claim 1 wherein the reaction is carried out inmethanol, ethanol, isopropanol, isobutanol, ethyl acetate, n-butylacetate, isopropyl acetate, isoamyl alcohol or 2-ethylhexanol as thesolvent.